The general aim is to gain knowledge of the cell membrane-associated contractile and motor apparatus, and the differences in organization of this apparatus in normal and in transformed (cancer) cells. Because cytochalasins selectively, potently and reversibly affect this system, in a major part of this study cytochalasins, especially cytochalasin D (CD), will be used as a probe of the membrane and its contractile structures and their interrelations. We intend to identify the sites and components to which radiocytochalasin D (H3-CD) is bound in the cell and its fractions; to correlate binding with content of contractile (and accessory or related) proteins; and to define the characteristics of the cytocholastin receptor(s). The biological properties of analogs of CD and polymer-bound cytochalasin will be evaluated as an adjunct of investigation of their mechanism of action. The role of the membrane lipid bilayer and direct effects of CD on model contractile systems will be explored. The influence of treatments that act in defined ways on cell membrane; on microfilament apparatus and cytoskeletal structures will be studied by examining the structure, filament distribution and H3-CD uptake of treated cells or fractions, in comparison with the effects of CD. We will especially compare nontransformed and the transformed (including epithelial) cells derived from them with respect to binding of H3-CD, their microfilament apparatus, and the differential effects of CD treatment on their membrane-associated contractile structures and on their behavior. We propose to investigate the basis for differences in the effects and for differential cytotoxicity of CD in normal cells and those exhibiting unregulated growth (cancer cells), as well as the selective lethality of combined cytochalasin and carcinostatic drug for cancer cells.